6v5b: Difference between revisions

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<StructureSection load='6v5b' size='340' side='right'caption='[[6v5b]], [[Resolution|resolution]] 3.70&Aring;' scene=''>
<StructureSection load='6v5b' size='340' side='right'caption='[[6v5b]], [[Resolution|resolution]] 3.70&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[6v5b]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6V5B OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6V5B FirstGlance]. <br>
<table><tr><td colspan='2'>[[6v5b]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6V5B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6V5B FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.7&#8491;</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ribonuclease_III Ribonuclease III], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.26.3 3.1.26.3] </span></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6v5b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v5b OCA], [http://pdbe.org/6v5b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6v5b RCSB], [http://www.ebi.ac.uk/pdbsum/6v5b PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6v5b ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6v5b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v5b OCA], [https://pdbe.org/6v5b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6v5b RCSB], [https://www.ebi.ac.uk/pdbsum/6v5b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6v5b ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/RNC_HUMAN RNC_HUMAN]] Ribonuclease III double-stranded (ds) RNA-specific endoribonuclease that is involved in the initial step of microRNA (miRNA) biogenesis. Component of the microprocessor complex that is required to process primary miRNA transcripts (pri-miRNAs) to release precursor miRNA (pre-miRNA) in the nucleus. Within the microprocessor complex, DROSHA cleaves the 3' and 5' strands of a stem-loop in pri-miRNAs (processing center 11 bp from the dsRNA-ssRNA junction) to release hairpin-shaped pre-miRNAs that are subsequently cut by the cytoplasmic DICER to generate mature miRNAs. Involved also in pre-rRNA processing. Cleaves double-strand RNA and does not cleave single-strand RNA. Involved in the formation of GW bodies.<ref>PMID:10948199</ref> <ref>PMID:14508493</ref> <ref>PMID:15589161</ref> <ref>PMID:15574589</ref> <ref>PMID:15531877</ref> <ref>PMID:15565168</ref> <ref>PMID:16751099</ref> <ref>PMID:16906129</ref> <ref>PMID:17159994</ref> [[http://www.uniprot.org/uniprot/DGCR8_HUMAN DGCR8_HUMAN]] Component of the microprocessor complex that acts as a RNA- and heme-binding protein that is involved in the initial step of microRNA (miRNA) biogenesis. Component of the microprocessor complex that is required to process primary miRNA transcripts (pri-miRNAs) to release precursor miRNA (pre-miRNA) in the nucleus. Within the microprocessor complex, DGCR8 function as a molecular anchor necessary for the recognition of pri-miRNA at dsRNA-ssRNA junction and directs DROSHA to cleave 11 bp away form the junction to release hairpin-shaped pre-miRNAs that are subsequently cut by the cytoplasmic DICER to generate mature miRNAs. The heme-bound DGCR8 dimer binds pri-miRNAs as a cooperative trimer (of dimers) and is active in triggering pri-miRNA cleavage, whereas the heme-free DGCR8 monomer binds pri-miRNAs as a dimer and is much less active. Both double-stranded and single-stranded regions of a pri-miRNA are required for its binding. Involved in the silencing of embryonic stem cells self-renewal.<ref>PMID:15589161</ref> <ref>PMID:15574589</ref> <ref>PMID:15531877</ref> <ref>PMID:16751099</ref> <ref>PMID:16906129</ref> <ref>PMID:16963499</ref> <ref>PMID:17159994</ref> 
[https://www.uniprot.org/uniprot/RNC_HUMAN RNC_HUMAN] Ribonuclease III double-stranded (ds) RNA-specific endoribonuclease that is involved in the initial step of microRNA (miRNA) biogenesis. Component of the microprocessor complex that is required to process primary miRNA transcripts (pri-miRNAs) to release precursor miRNA (pre-miRNA) in the nucleus. Within the microprocessor complex, DROSHA cleaves the 3' and 5' strands of a stem-loop in pri-miRNAs (processing center 11 bp from the dsRNA-ssRNA junction) to release hairpin-shaped pre-miRNAs that are subsequently cut by the cytoplasmic DICER to generate mature miRNAs. Involved also in pre-rRNA processing. Cleaves double-strand RNA and does not cleave single-strand RNA. Involved in the formation of GW bodies.<ref>PMID:10948199</ref> <ref>PMID:14508493</ref> <ref>PMID:15589161</ref> <ref>PMID:15574589</ref> <ref>PMID:15531877</ref> <ref>PMID:15565168</ref> <ref>PMID:16751099</ref> <ref>PMID:16906129</ref> <ref>PMID:17159994</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Metazoan microRNAs require specific maturation steps initiated by Microprocessor, comprising Drosha and DGCR8. Lack of structural information for the assembled complex has hindered an understanding of how Microprocessor recognizes primary microRNA transcripts (pri-miRNAs). Here we present a cryoelectron microscopy structure of human Microprocessor with a pri-miRNA docked in the active site, poised for cleavage. The basal junction is recognized by a four-way intramolecular junction in Drosha, triggered by the Belt and Wedge regions that clamp over the ssRNA. The belt is important for efficiency and accuracy of pri-miRNA processing. Two dsRBDs form a molecular ruler to measure the stem length between the two dsRNA-ssRNA junctions. The specific organization of the dsRBDs near the apical junction is independent of Drosha core domains, as observed in a second structure in the partially docked state. Collectively, we derive a molecular model to explain how Microprocessor recognizes a pri-miRNA and accurately identifies the cleavage site.


Cryo-EM Structures of Human Drosha and DGCR8 in Complex with Primary MicroRNA.,Partin AC, Zhang K, Jeong BC, Herrell E, Li S, Chiu W, Nam Y Mol Cell. 2020 Mar 21. pii: S1097-2765(20)30109-X. doi:, 10.1016/j.molcel.2020.02.016. PMID:32220646<ref>PMID:32220646</ref>
==See Also==
 
*[[Ribonuclease 3D structures|Ribonuclease 3D structures]]
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6v5b" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Ribonuclease III]]
[[Category: Chiu W]]
[[Category: Chiu, W]]
[[Category: Herrell E]]
[[Category: Herrell, E]]
[[Category: Jeong B]]
[[Category: Jeong, B]]
[[Category: Li S]]
[[Category: Li, S]]
[[Category: Nam Y]]
[[Category: Nam, Y]]
[[Category: Partin A]]
[[Category: Partin, A]]
[[Category: Zhang K]]
[[Category: Zhang, K]]
[[Category: Dgcr8]]
[[Category: Drosha]]
[[Category: Microprocessor]]
[[Category: Primary microrna]]
[[Category: Rna binding protein]]
[[Category: Rna binding protein-rna complex]]

Latest revision as of 17:35, 6 March 2024

Human Drosha and DGCR8 in complex with Primary MicroRNA (MP/RNA complex) - Active stateHuman Drosha and DGCR8 in complex with Primary MicroRNA (MP/RNA complex) - Active state

Structural highlights

6v5b is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Electron Microscopy, Resolution 3.7Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

RNC_HUMAN Ribonuclease III double-stranded (ds) RNA-specific endoribonuclease that is involved in the initial step of microRNA (miRNA) biogenesis. Component of the microprocessor complex that is required to process primary miRNA transcripts (pri-miRNAs) to release precursor miRNA (pre-miRNA) in the nucleus. Within the microprocessor complex, DROSHA cleaves the 3' and 5' strands of a stem-loop in pri-miRNAs (processing center 11 bp from the dsRNA-ssRNA junction) to release hairpin-shaped pre-miRNAs that are subsequently cut by the cytoplasmic DICER to generate mature miRNAs. Involved also in pre-rRNA processing. Cleaves double-strand RNA and does not cleave single-strand RNA. Involved in the formation of GW bodies.[1] [2] [3] [4] [5] [6] [7] [8] [9]

See Also

References

  1. ↑ Wu H, Xu H, Miraglia LJ, Crooke ST. Human RNase III is a 160-kDa protein involved in preribosomal RNA processing. J Biol Chem. 2000 Nov 24;275(47):36957-65. PMID:10948199 doi:http://dx.doi.org/10.1074/jbc.M005494200
  2. ↑ Lee Y, Ahn C, Han J, Choi H, Kim J, Yim J, Lee J, Provost P, Radmark O, Kim S, Kim VN. The nuclear RNase III Drosha initiates microRNA processing. Nature. 2003 Sep 25;425(6956):415-9. PMID:14508493 doi:http://dx.doi.org/10.1038/nature01957
  3. ↑ Landthaler M, Yalcin A, Tuschl T. The human DiGeorge syndrome critical region gene 8 and Its D. melanogaster homolog are required for miRNA biogenesis. Curr Biol. 2004 Dec 14;14(23):2162-7. PMID:15589161 doi:10.1016/j.cub.2004.11.001
  4. ↑ Han J, Lee Y, Yeom KH, Kim YK, Jin H, Kim VN. The Drosha-DGCR8 complex in primary microRNA processing. Genes Dev. 2004 Dec 15;18(24):3016-27. Epub 2004 Dec 1. PMID:15574589 doi:10.1101/gad.1262504
  5. ↑ Gregory RI, Yan KP, Amuthan G, Chendrimada T, Doratotaj B, Cooch N, Shiekhattar R. The Microprocessor complex mediates the genesis of microRNAs. Nature. 2004 Nov 11;432(7014):235-40. Epub 2004 Nov 7. PMID:15531877 doi:10.1038/nature03120
  6. ↑ Zeng Y, Yi R, Cullen BR. Recognition and cleavage of primary microRNA precursors by the nuclear processing enzyme Drosha. EMBO J. 2005 Jan 12;24(1):138-48. Epub 2004 Nov 25. PMID:15565168 doi:http://dx.doi.org/10.1038/sj.emboj.7600491
  7. ↑ Han J, Lee Y, Yeom KH, Nam JW, Heo I, Rhee JK, Sohn SY, Cho Y, Zhang BT, Kim VN. Molecular basis for the recognition of primary microRNAs by the Drosha-DGCR8 complex. Cell. 2006 Jun 2;125(5):887-901. PMID:16751099 doi:10.1016/j.cell.2006.03.043
  8. ↑ Pauley KM, Eystathioy T, Jakymiw A, Hamel JC, Fritzler MJ, Chan EK. Formation of GW bodies is a consequence of microRNA genesis. EMBO Rep. 2006 Sep;7(9):904-10. Epub 2006 Aug 11. PMID:16906129 doi:7400783
  9. ↑ Faller M, Matsunaga M, Yin S, Loo JA, Guo F. Heme is involved in microRNA processing. Nat Struct Mol Biol. 2007 Jan;14(1):23-9. Epub 2006 Dec 10. PMID:17159994 doi:10.1038/nsmb1182

6v5b, resolution 3.70Å

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